Cited by 501Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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Intrathecal inflammation precedes development of Alzheimer's disease

Open access

Tarkowski, E·2003·Journal of Neurology, Neurosurgery & Psychiatry

DOI 10.1136/jnnp.74.9.1200PMC PMC1738668

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Abstract

OBJECTIVES: To analyse the cerebrospinal fluid (CSF) values of the proinflammatory cytokines, interleukin 1beta (IL1beta), tumour necrosis factor alpha (TNFalpha), GM-CSF, of the anti-inflammatory cytokine TGFbeta, of tau protein, a marker for neurodegeneration, and of beta amyloid (Abeta), a protein involved in the formation of senile plaques, in prospectively followed up patients with mild cognitive impairment (MCI). METHODS: Analyses of CSF levels of TNFalpha, IL1beta, GM-CSF, TGFbeta, betaa, and tau protein were performed using ELISA in 56 patients with MCI who were followed up prospectively and in 25 age matched, healthy controls. RESULTS: Patients with MCI displayed significantly higher levels of TNFalpha and tau protein and significantly lower levels of TGFbeta and Abeta compared with the healthy controls. After nine months of follow up, 25 patients still displayed MCI while the remaining 31 patients had progressed to Alzheimer's disease (AD). Only MCI patients who progressed to AD at follow up, showed significantly higher CSF levels of TNFalpha than controls. In addition, reduced CSF-Abeta42 levels were only found in MCI patients that progressed to AD, further supporting the notion that disturbed metabolism of Abeta is an early finding in AD. CONCLUSIONS: These results demonstrate increased production of the proinflammatory cytokine, TNFalpha and decreased production of the anti-inflammatory cytokine TGFbeta in patients with MCI at risk to develop AD, suggesting a propensity towards inflammation in this patient group and indicating that CNS inflammation is a early hallmark in the pathogenesis of AD.

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Additional file 8 of TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer's disease hippocampus
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Additional file 7 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
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Additional file 6 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
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Additional file 1 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
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Additional file 4 of Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease
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Additional file 3 of Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease
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Additional file 9 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
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Additional file 13 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
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Additional file 5 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
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Additional file 4 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694834
Additional file 8 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
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Additional file 12 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
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Additional file 1 of Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease
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Additional file 10 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694852
Additional file 3 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694831
Additional file 7 of TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer's disease hippocampus
Jayaraman, A., Htike, T. T., James, R., Picón, C., & Reynolds, R. (2021) · Figshare · doi:10.6084/m9.figshare.16778487
Additional file 2 of Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease
Munawara, U., Catanzaro, M., Xu, W., Tan, C., Hirokawa, K., Bosco, N., Dumoulin, D., Khalil, A., Larbi, A., Lévesque, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14821082
Additional file 2 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694828
Additional file 11 of Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice
Jagadeesan, N., Roules, G. C., Chandrashekar, D. V., Yang, J., Kolluru, S., & Sumbria, R. K. (2024) · Figshare · doi:10.6084/m9.figshare.26694855
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(2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2305-5839.2015.03.49 · Cited by 1,288

Authors: Tarkowski, E.
Affiliations: University of Gothenburg (SE)
Corresponding author: Tarkowski, E
Venue: Journal of Neurology, Neurosurgery & Psychiatry
Publisher: BMJ
Published: 2003-09-01
Volume: 74
Issue: 9
Pages: 1200-1205
ISSN: 0022-3050 (ISSN-L)
DOI: 10.1136/jnnp.74.9.1200
PMC: PMC1738668
OpenAlex: W2071728536
Cited by: 501
References: 53
Citations by year: 2026: 16 · 2025: 17 · 2024: 45 · 2023: 28 · 2022: 43 · 2021: 51 · 2020: 23 · 2019: 30 · 2018: 32 · 2017: 23 · 2016: 18 · 2015: 16 · 2014: 14 · 2013: 13 · 2012: 18
FWCI: 6.52
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Rune och Ulla Amlövs Stiftelse för Neurologisk och Reumatologisk Forskning
Hjärt-Lungfonden
Göteborgs Läkaresällskap
Svenska Läkaresällskapet
Stiftelsen Konung Gustaf V:s 80-årsfond
Medical Research Council
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Alzheimer's disease, mild cognitive impairment, cerebrospinal fluid biomarkers, intrathecal inflammation, inflammatory cytokines, TNF-α, IL-1β, GM-CSF, TGF-beta, tau protein, amyloid-beta, amyloid metabolism, neuroinflammation, disease progression
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Central Nervous System, Cognition Disorders, Female, Humans, Inflammation, Interleukin-1, Male, Middle Aged, Prospective Studies, Risk Factors, Tumor Necrosis Factor-alpha, Granulocyte-Macrophage Colony-Stimulating Factor, Amyloid beta-Peptides, tau Proteins, Plaque, Amyloid

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Intrathecal inflammation precedes development of Alzheimer's disease

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